Renal handling of radiolabelled human cystatin C in the rat

Abstract

Serum cystatin C concentration correlates negatively with glomerular filtration rate as well as or better than that of serum creatinine, suggesting a constant formation, and elimination from extracellular fluid mainly by glomerular filtration. It is not known, however, how well the renal plasma clearance of this 13-kDa basic polypeptide matches the glomerular filtration rate. This was investigated in rats during control conditions and after reduced renal perfusion pressure. ¹²⁵I-cystatin C and an indicator for glomerular filtration (⁵¹Cr-EDTA or ¹³¹I-aprotinin) were injected intravenously. The renal accumulation and urinary excretion of the tracers were recorded in periods of 2.5 to 20.0 min. The renal plasma clearance of ¹²⁵I-cystatin C (C_cy) based on the renal content of ¹²⁵I correlated well with the glomerular filtration rate (C_cr-edta) in periods up to 6 min; i.e. C_cy=0.94 × C_cr-EDTA, r=0.99. Less than 0.5% of the filtered amount appeared in the urine. During more prolonged periods, C_cy increasingly underestimated glomerular filtration rate, reaching about 0.4 ×C_cr-EDTA in a 20-min period. Free ¹²⁵I relative to total plasma ¹²⁵I activity increased from about 2% at 5 min to about 70% at 20 min. In nephrectomized rats, free ¹²⁵I accumulated in plasma at a slower rate, accounting for about 15% of the total activity 20 min after injection of ¹²⁵I-cystatin C. We conclude that cystatin C is (a) mainly removed from the extracellular fluid by the kidneys, (b) practically freely filtered in the glomeruli, and (c) completely absorbed and rapidly broken down by the proximal tubular cells.

Key Words:

• creatinine
• glomerular filtration rate
• glomerular sieving
• polypeptide
• proximal tubules
• renal clearance
• renal polypeptide catabolism